Since the discovery of thienamycin, it has been recently proved that carbapenem or penem derivatives having a 1-hydroxyethyl group at the 6-position of their skeleton possess excellent antimicrobial activities and are useful as medicines, and studies on syntheses thereof have been extensively conducted.
The present inventors have made various investigations to develop an effective process for producing carbapenem or penem derivatives having a 1-hydroxyethyl group at their 6-position and, as a result, found that 3-acetyl-2-azetidinone-4-carboxylic acid derivatives or 3-(1-hydroxyethyl)-2-azetidinone-4-carboxylic acid derivatives that are important intermediates for these carbapenem or penem derivatives can easily and effectively be produced, and that these derivatives can be converted into the desired carbapenem or penem derivatives.
A conventional process for preparing N-protected-3-acetyl or 3-(1-hydroxyethyl)-2-azetidinone-4-carboxylic acid derivatives comprises introducing an acetyl group or a 1-hydroxyethyl group to the 3-position of 3-unsubstituted 2-azetidinone, for example, by aldol condensation in the presence of a strong base as disclosed in Tetrahedron Letters, 23 (22), 2293 (1982), and the like. However, such known processes are disadvantageous in terms of number of steps involved, workability, etc.
To the contrary, the process of the present invention makes it possible to produce N-protected-3-acetyl or 3-(1-hydroxyethyl)-2-azetidinone-4-carboxylic acid derivatives at high efficiency through very simple operations.